tbuckley/cabot-search huggingface dataset:
Racial and socioeconomic disparities among patients with chronic lymphocytic leukemia: Analysis of Surveillance, Epidemiology, and End Results program data.
Authors: Adam Kittai, Ying Huang, James L. Fisher, Seema Bhat, Michael R. Grever, Electra D. Paskett, Kerry Anne Rogers, Jennifer Ann Woyach
Journal: Journal of Clinical Oncology (2022)

7542 Background: Therapy for chronic lymphocytic leukemia (CLL) has changed dramatically over the past 20 years. With the cost of new therapies and rapid practice changes, it is unclear if patients (pts) are benefiting equally from this progress. We assessed Surveillance, Epidemiology, and End Results (SEER) program data to determine how race and socioeconomic status (SES) affect survival for pts with CLL. Methods: CLL cases reported to 18 SEER Program registries from 2006 – 2018 were included. Pt characteristics such as age at diagnosis (dx), sex, year (yr) of dx, race, and SES as determined by rural/urban census tract residence (RUCA), and neighborhood (as represented by the Yost Index, a composite measure of 7 variables assessing different aspects of the SES of a census tract) were collected and analyzed. Multivariable cox regression (MVA) was used to determine adjusted odds of survival. Two separate databases were utilized, one which included data to 2018, and another which contained SES data but only had data available to 2016. Results: 46,605 cases from 2009 – 2018 were identified without SES data. The median age was 70 yrs, 60% were male, and there was an even distribution of patients diagnosed with CLL annually from 2009 – 2018. Of the cases with race reported, 89.9% were white, 7.3% Black, 2.4% Asian/Pacific islander, and 0.3% American Indian/Alaska Native. After a median follow up of 47 months, the median 3, 5, and 10 yr overall survival (OS) was 79.5%, 69.5%, and 48.8%, respectively. MVA showed Black race (HR 1.5, 95% CI 1.4 – 1.6) as the strongest independent prognostic variable for worse OS controlling for yr of dx, suggesting race was a significant factor in OS in the era of modern therapies. Using the linked RUCA and Yost tertiles for SES, 47,867 cases of CLL from 2006 – 2016 were analyzed. Median age, sex, and race distribution were similar to the prior analysis. MVA showed American Indian/Alaska Native, and Black race as independent prognostic variables for worse OS, and Yost group 2 and 3, representing higher SES, were found to be significant independent prognostic variables for improved OS (Table 1). In this analysis, race remained an independent variable for worse OS after controlling for SES. Conclusions: Black race and low SES are prognostic of OS in CLL. Further research is needed to determine whether this is due to access to therapy, quality of care, social determinants of heath, or disease biology.[Table: see text]
DIPG-46. Radiation induced senescence in diffuse intrinsic pontine glioma cells reveals selective vulnerability to Bcl-XL inhibition
Authors: Ashley Vardon, Romain Guiho, Diana Carvalho, Jessica Boult, Rebecca Carter, Yura Grabovska, Alan Mackay, Guangrong Zheng, Daohong Zhou, Crispin Hiley, Mark Lythgoe, Chris Jones, Darren Hargrave, Juan-Pedro Martinez-
Journal: Neuro-Oncology (2022)

Abstract Diffuse intrinsic pontine glioma remains a devastating condition with a dismal five year survival rate less than 5%. New approaches for treating this aggressive disease are critical to driving progress. Conventional radiotherapy remains the cornerstone of treatment, with no chemotherapeutic agent found to improve survival. However, radiotherapy is often delivered as a palliative treatment, and disease often recurs 3-6 months after. Radiation causes DNA damage and oxidative stress yielding a senescent state of replicative arrest in susceptible cells. However, increasing evidence demonstrates malignant cells can escape senescence leading to tumour recurrence. Targeted ablation of non-replicating senescent tumour cells following radiation could negate tumour recurrence. It remains unknown whether DIPG undergoes senescence following radiation, and furthermore, whether senolytics can be utilised to target senescent DIPG cells. We employed radiation to induce a senescent state in primary human DIPG cell lines. Senescence was confirmed using SA-β-gal staining, lack of EdU incorporation and qRT-PCR to characterise the SASP in three primary human DIPG cell lines. RNA-sequencing on DIPG cells following radiation revealed senescence and SASP signatures. Likewise, expression of senescence markers has been detected in human tumours. Viable cells that survive radiation were then utilised to screen candidate senolytic drugs, only Bcl-XL inhibitors demonstrated reproducible senolytic activity in radiation treated DIPG cells. In addition, Bcl-XL degradation using PROTACs (proteolysis targeting chimeras) resulted in a significant increase in senolysis of susceptible tumour cells. Conversely, Bcl-2 inhibitors failed to show any consistent senolytic activity. We are currently performing preclinical studies in the mouse to test the efficiency of senolytics against DIPG. These results demonstrate future possibilities of targeting radiation induced senescence in DIPG, using novel senolytic therapies and highlight Bcl-XL dependency as a potential vulnerability of surviving DIPG cells following exposure to radiation.
Identification of novel genes influencing eosinophil-specific protein levels in asthma families
Authors: Raphaël Vernet, Régis Matran, Farid Zerimech, Anne-Marie Madore, Marie-Eve Lavoie, Pierre-Alexandre Gagnon, Hamida Mohamdi, Patricia Margaritte-Jeannin, Valérie Siroux, Marie-Hélène Dizier, Florence Demenais, Catherine Laprise, Rachel Nadif, Emmanuelle Bouzigon
Journal: Journal of Allergy and Clinical Immunology (2022)
Trends in early phase clinical trials: A tale of exponential economic growth and access.
Authors: Neha K. Reddy, Niamh Coleman, Vivek Subbiah
Journal: Journal of Clinical Oncology (2022)

e18504 Background: There has been exponential economic growth in the BRIC (Brazil, Russia, India and China) nations in recent years, and outsourcing of clinical trials to these countries has occurred in tandem. Our study aimed to assess the current status of early phase oncology clinical trial recruitment in the BRIC countries, to assess the impact of these emerging economies and global markets in health care. Methods: We reviewed the open-access clinical trial registry, clinicaltrials.gov, for registered interventional recruiting early phase trials (Phase I/II) in the BRIC countries in adults and analyzed each country separately and collectively. We extracted descriptive data and established a database and proceeded to perform literature review and examine trends in early phase clinical trials. Results: We identified 888 recruiting early phase clinical trials in BRIC countries; China had 95% (842/888) of the trials, Brazil 1.5% (13/888), Russia 3.4% (30/888) and India 0.34% (3/888). For tumor specific studies, gastrointestinal (17%, 148/888), lung 11% (94/888) and breast (17%, 53/888) cancers were the most studied. Most trials were industry-sponsored (76%, 675/888); and most conducted in a single country (95%, 846). Industry-sponsored studies comprised 96% in China (635/842), 87% in Russia (26/30), 92% in Brazil (12/13), 67% (2/3) in India. Overall, immunotherapy agents in single and combination treatment strategies were the most common agent under investigation, with novel therapies such as CAR T-cell therapy (eg. CAR-T/TCR NK-CAR CAR-T/TCR-T Cell) being increasingly used in China (168 single agent trials, 30 trials in combination: 24% of trials in China). In contrast, CAR T-cell therapy trials were not yet in BRIC nations outside of China. Combination studies were frequent (33%, 293/888), and included a variety of combination strategies utilizing targeted therapies, immunotherapies, chemotherapies, antibody drug conjugates and novel biologics. Conclusions: Despite the economic explosion and shift of non-oncology clinical trials to BRIC nations, US and Europe continue to dominate in the design and conduct of early phase clinical trials in hematology and oncology. However, there has been exponential growth in early phase trial testing in China, which now accounts for 18.5% of the world’s population and has the majority (95%) of trials in BRIC nations. Contrastingly, India, which accounts for 17.7% of world’s population, has &lt; 1% of BRIC nation trials. In keeping with trends in the US and Europe, there is a dominance of industry-sponsored studies in BRIC countries. Globally, early phase trials are increasing in their complexity with ongoing interest in immune modulation as a treatment strategy.
Understanding women’s perspectives on breast cancer is essential for early breast cancer diagnosis and to avoid diagnosis delay: A mixed method study.
Authors: Uma V Sankar, Narayanankutty Edavalath Warrier, Rakhi T S, Roshna Wilson
Journal: Journal of Clinical Oncology (2022)

e24036 Background: Breast Cancer is the most common cancer in women worldwide. Since 2017, MVR Cancer Centre is a tertiary care hospital, New national guidelines focused on clinical breast exam and mammogram require that women be aware of and seek care for breast concerns. Therefore, this study aims to understand women’s perspective on breast cancer diagnosis. Methods: Sequential explanatory method was used to satisfy the objectives of the study. A crossectional survey was conducted to conveniently sampled women aged 30 and older to assess women’s perspectives on breast cancer and care-seeking behavior. We did a qualitative interview among selected breast cancer women to know about the reasons of delayed diagnosis and treatment delay. Results: Among 378 women with a median age of 49 (IQR: 34–62) years, 73% have heard of cancer and 30% have received self-breast examination. Women self-evaluated their knowledge of breast cancer (from 1-none to 10-extremely knowledgeable) with a median response of 3 (IQR: 1–4). Only 24% felt they knew any signs or symptoms of breast cancer. Encouragingly, 42% of women were fairly-to-very confident they would notice changes in their breasts, with 22% of women practicing self-breast examination and 8% reporting they had received a past breast exam. Overall, 64% said they would be somewhat-to-very likely to seek care if they noticed breast changes, with 98% noting severity of symptoms as a motivator. However, altered sexuality (43%), fear of losing a breast - Womanhood(70%) and fear of a poor diagnosis (48%) were most frequent barriers to care seeking. In assessing knowledge of risk factors, about 70% of women did not know any risk factors for breast cancer whereas 12% of women believed long term contraceptive use a risk factor. However, 37% and 35% of women did not think that family history or being older were risk factors, respectively. Social recognition as woman, existence of womanhood, cost of treatment and related financial burden and fear of complications and death are the themes emerged from the qualitative study. Conclusions: The success of efforts to improve early diagnosis in a setting without population-based screening depends on women being aware of breast cancer signs and symptoms, risks, and ultimately seeking care for breast concerns. Unfortunately, most women said they would seek care if they noticed a severity in the signs and symptoms of cancer, but the low levels of cancer knowledge, symptoms, and common risk factors highlight the need for targeted community education and awareness campaigns.
SEAMARK: Randomized phase 2 study of pembrolizumab + encorafenib + cetuximab versus pembrolizumab alone for first-line treatment of <i>BRAF</i> V600E-mutant and microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC).
Authors: Scott Kopetz, Tanios S. Bekaii-Saab, Takayuki Yoshino, Chin-Hee Chung, Xiaosong Zhang, Josep Tabernero
Journal: Journal of Clinical Oncology (2022)

TPS3634 Background: Among patients with MSI-H/dMMR CRC, BRAF mutations occur in approximately 30%. MSI-H/dMMR and BRAF mutations are both associated with poor prognosis; in patients who have both biomarkers, poor prognosis is thought to be driven by the BRAF mutation. Pembrolizumab is indicated for the treatment of patients with MSI-H/dMMR unresectable or metastatic CRC (mCRC). The BRAF inhibitor encorafenib, in combination with cetuximab, is indicated for previously treated patients with BRAF V600E-mutant mCRC. Currently, there are no first-line treatment options indicated specifically for patients with both MSI-H/dMMR and BRAF V600E-mutant mCRC. To assess the safety and efficacy of combining pembrolizumab with encorafenib + cetuximab, the SEAMARK study (NCT05217446) will evaluate this combination vs pembrolizumab alone in patients with previously untreated BRAF V600E-mutant MSI-H/dMMR mCRC. Methods: SEAMARK is an open-label, multicenter, randomized, phase 2 study. Approximately 104 patients (randomized 1:1; stratified by Eastern Cooperative Oncology Group Performance Status [ECOG PS] 0 vs 1) will receive either pembrolizumab + encorafenib + cetuximab or pembrolizumab. Enrolled patients must be aged ≥16 or ≥18 years (per country-specific regulations) and have previously untreated BRAF V600E-mutant MSI-H/dMMR mCRC; measurable disease (Response Evaluation Criteria in Solid Tumors v1.1); ECOG PS 0 or 1; and adequate bone marrow, hepatic, and renal function. Patients who received prior treatment with BRAF/EGFR inhibitors or immune checkpoint inhibitors, or who have brain metastases (unless radiologically stable) or RAS mutation (or unknown RAS status), will be excluded. The primary endpoint is investigator-assessed progression-free survival. Secondary endpoints include safety and tolerability, overall survival, objective response rate, duration of response, and quality of life. Enrollment will begin in April 2022. Clinical trial information: NCT05217446.
Successful biosimilar adoption in oncology: strategic approach to system standardization.
Authors: Suwicha Limvorasak, Crystal Leung Dobbs, James Kim, Edwin Melencio Posadas, Hilary Teaford, Marcio A. Diniz, Andre Rogatko, Bruce Vinson, Leanne Sakamoto, Vipul Patel, Robert A. Figlin, Rita Shane, Karen L. Reckamp
Journal: Journal of Clinical Oncology (2022)

e18605 Background: In the United States, therapeutic substitution with oncologic biosimilars offer opportunities to reduce the rising costs of cancer care while improving access to safe and effective treatment. Current challenges include integration into clinical practice, state laws for biosimilar interchangeability and payer reimbursement policies. Methods: We developed an approach to standardize biosimilar utilization across our oncology enterprise by leveraging the electronic health record to integrate with clinical algorithm pathways and financial information. Institutionally preferred biosimilars drugs were selected through the oncology Pharmacy &amp; Therapeutics committee as part of the formulary process. Physicians were permitted to opt-out of substitution within the electronic order sets. Patients were divided into two groups based as 1) main medical center 2) affiliated sites to assess feasibility of the enterprise-wide substitution, defined as an 80% compliance rate at the main medical center and a 75% compliance rate at the affiliates sites. This provided a minimum detectable difference of 5.7% and 8.9%, respectively using an exact one-sided Binomial test with 80% of power at 2.5% significance level with Sidak correction. Results: Between January and December 2021, a total of 811 cancer patients who initiated treatment with bevacizumab, rituximab or trastuzumab were identified, of whom 535 were eligible for this analysis (age 18-96; 61% female, 39% male). The overall substitution rate to biosimilars was 83% (76%-97%) compared to baseline of 55%, representing a 51% improvement. The conversion rate was higher at the main medical center compared to the affiliated sites (85% vs. 81%). Among 92 patients who did not have substitution to biosimilars, the most common reasons were off-label indication (35%), patient assistance program (17%), payer preferred alternative brand (15%) and clinician preferred reference brand (12%). Four patients (&lt; 1%) were not converted due to infusion reactions possibly related to biosimilars. Based on the wholesale acquisition cost, we estimate reduction in direct spending of $1.2 million per month or an average 23% cost savings. Conclusions: This real-world data suggest use of an integrated electronic health record to standardize biosimilar utilization in oncology and reduce costs. This approach leverages existing infrastructure for successful biosimilar adoption in oncology while preserving quality and safety.[Table: see text]
CaboMain: A phase 2 study of cabozantinib as a maintenance agent in patients with ultra-high risk pediatric solid tumors.
Authors: Nilay Shah
Journal: Journal of Clinical Oncology (2022)

TPS10060 Background: Patients with relapsed or refractory pediatric solid tumors have one-year progression-free survival (PFS) &lt;25% even if a remission is achieved [1-9]. Maintenance treatments may extend survival for these patients but have not been tested. Many tyrosine kinase inhibitors (TKIs) target oncogenic pathways active in pediatric cancers and are being evaluated in children with cancer. The multitargeted TKI cabozantinib inhibits MET, VEGFR, AXL, RET, ROS1, KIT, TRKB, FLT3, and TIE2. Preclinical studies and clinical use suggest that cabozantinib may be active against childhood cancers [10-20]. A pediatric Phase 1 study defined a dose of 40 mg/m 2 /day[21], currently used in an ongoing pediatric Phase 2 study for measurable relapsed/refractory solid tumors, NCT02867592. However, cabozantinib has not been tested as a maintenance agent against cancers in children. We hypothesize that cabozantinib, in patients with ultra-high-risk pediatric solid tumors with minimal disease burden, can prevent recurrent tumor formation or induce a durable remission. Methods: Trial Design: Single arm, open-label, multisite investigator-initiated Phase 2 trial for patients with a “best response,” defined as no progression at least 28 days after end of prior therapy. Primary objective: Evaluate the effect of cabozantinib administered for up to 12 months on 1-year PFS. Statistical design and measure: Bayesian time-to-event optimal phase 2 design with a single interim analysis designed to detect 20% increase in PFS at 1 year with 80% power. Secondary objectives include 2- and 5-year PFS; 1-, 2-, and 5- year OS, duration of response, and safety and tolerability. Exploratory objectives include patient-reported outcomes, predictive biomarkers, PK and PD measurements. Treatment: Patients will take cabozantinib tablets on a continuous dosing schedule, partitioned into 28-day cycles, at an initial dose of 40 mg/m2/day (per dosing nomogram), for up to 365 days. Assessments are defined; radiographic assessment every 3 cycles. Dose modifications will be based on toxicities per protocol. Patients will continue on therapy until progression, toxicities not relieved by dose reduction, or end of planned therapy. Major eligibility criteria: Three strata: Neuroblastoma with residual disease at end of upfront therapy (“Best Response 1”, BR1) or after any relapse, n=36. Pediatric CNS tumors, defined in the protocol, n=30. Other pediatric solid tumors, as defined in the protocol, n=36. Patients must be ≥ 18 months and ≤40 years of age at enrollment, have completed prior therapy ≥ 4 weeks and ≤ 12 weeks prior to enrollment and demonstrate radiographic BR at time of enrollment. Measurable or evaluable disease is not required. Enrollment: Protocol is open to enrollment as of February 12, 2022. At time of abstract submission, we have not yet enrolled the first patient. Clinical trial information: NCT05135975.
Exploring the value of using patient-oriented mri reports in clinical practice
Authors: N. Perlis, A. Finelli, M. Lovas, A. Lund, A. Di Meo, K. Lajkosz, A. Berlin, J. Papadakos, S. Ghai, D. Deniffel, E. Meng, D. Wiljer, S. Alibhai, V. Bakas, A. Badzynski, O. Lee, J. Cafazzo, M. Haider
Journal: European Urology (2022)
Addition of carfilzomib as a third agent in lenalidomide-refractory multiple myeloma: Switching from doublet to triplet.
Authors: Claudio Cerchione, Davide Nappi, Lucio Catalano, Sonia Ronconi, Delia Cangini, Michela Ceccolini, Gerardo Musuraca, Giovanni Martinelli
Journal: Journal of Clinical Oncology (2022)

e20002 Background: Carfilzomib is an epoxyketone proteasome inhibitor of second generation, proved to be effective and safe in relapsed and refractory Multiple Myeloma (rrMM), in combination with dexamethasone or lenalidomide and dexamethasone. In this retrospective observational trial, it has been evaluated efficacy and safety of carfilzomib, in combination with lenalidomide-dexamethasone (KRD) as salvage regimen in patients with rrMM, refractory to lenalidomide, where lenalidomide-based regimens have no proven efficacy. Methods: 41 patients (23 M/18 F), with rrMM, median age at diagnosis 63.7 years (r. 43-82), median age at start of treatment 67 years (r. 48-84) previously treated with several lines of treatments (median 3, r. 2-11), underwent to KRD regimen (ASPIRE trial schedule) for a median treatment cycles of 8 (r 2-18). ISS was equally distributed, and all patients had previously been treated with bortezomib and IMIDs, and were refractory to this agents. 61% (19/31) of them had undergone at least to a single ASCT. Results: According to IMWG criteria, after a median follow-up of 9 months (r. 2-18), ORR was 68,2% (28/41: 9 CR, 12 VGPR, 7 PR) with 5 progressive diseases (PD) and 8 patients in stable disease (SD): this can be considered as an impressive result in this subset of rrMM patients, refractory to lenalidomide. In particular, for 11 patients, KRD was, after having achieved at least a PR, a bridge to second/third autologous SCT. Median time to response was 1.3 months (r.1-4), median OS from diagnosis was 62 months (r. 9-170), median OS from start of Carfilzomib was 11 months (r. 2-18). Carfilzomib was well tolerated, with grade 2 anemia in 39%(16/41) of patients, successfully managed by ESAs, without necessity of blood transfusions; 29% (12/41) grade 3-4 neutropenia (pegfilgrastim in primary prophylaxis was given, no ospedalization was required, no septic shocks were observed); 34% (14/41) grade 2, 21% (9/41) grade 3 and 12% (5/41) grade 4 thrombocytopenia, without hemorrhagic events and transfusion-dependency. Moreover, it was observed pneumonia in 39% (16/41) of patients, treated by common antibiotic drugs and always solved. A cardiac monitoring was performed for all patients: hypertension (grade 2-3) in 34% (14/41) of patients; fatigue in 39% (16/31) of patients. Conclusions: Carfilzomib-Lenalidomide-Dexamethasone has shown significant efficacy in a particularly severe setting of patients, relapsed and refractory to all available therapeutic resources, also lenalidomide, and it could be considered as a bridge to a second autologous or allogenic SCT. Clinical trial information: A108.